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C Bishop

Publications and source records attributed to C Bishop.

At least 19 recordsLinked to original sources
PubMed2001

Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene.

Proteins encoded by the human CYP3A genes metabolize every second drug currently in use. The activity of CYP3A gene products in the general population is highly variable and may affect the efficacy and safety of drugs metabolized by these enzymes. The mechanisms underlying this variability are poorly understood, but they include gene induction, protein inhibition and unknown genetic polymorphisms. To better understand the regulation of CYP3A expression and to provide a basis for a screen of genetic polymorphisms, we determined and analysed the sequence of the human CYP3A locus. The 231 kb locus sequence contains the three CYP3A genes described previously (CYP3A4, CYP3A5 and CYP3A7), three pseudogenes as well as a novel CYP3A gene termed CYP3A43. The gene encodes a putative protein with between 71.5% and 75.8% identity to the other CYP3A proteins. The highest expression level of CYP3A43 mRNA is observed in the prostate, an organ with extensive steroid metabolism. CYP3A43 is also expressed in several other tissues including liver, where it can be induced by rifampicin. CYP3A43 transcripts undergo extensive splicing. The identification of a new member of the CYP3A family and the characterization of the full CYP3A locus will aid efforts to identify the genetic variants underlying its variable expression. This, in turn, will lead to a better optimization of therapies involving the numerous substrates of CYP3A proteins.

Amino Acid Sequence↗
PubMed2000

Posterodorsal amygdala lesions reduce feeding stimulated by 8-OH-DPAT.

Injections of the serotonin (5-HT)(1A) agonist, 8-hydroxy-2(di-n-propylamino)tetralin, (8-OH-DPAT), either systemically or into the midbrain raphe nuclei, elicit food intake in otherwise satiated rats. Lesions of the paraventricular nucleus of the hypothalamus are well known for producing long-term overeating, but past research has excluded this site as a potential locus for short-term 8-OH-DPAT feeding effects. More recent work shows that small lesions of the posterodorsal amygdala (PDA) elicit overeating in their own right. Since this and related regions of the amygdala receive 5-HT innervations from the dorsal raphe nucleus (DRN), we determined if PDA lesions might alter feeding after injecting 8-OH-DPAT into this midbrain region. Adult female rats received either bilateral electrolytic lesions of the PDA or sham lesions. After recording weight gains for over 1 month, all rats were implanted with DRN cannulae, then randomly tested every 3-4 days for 1 h intake of standard lab chow after 0, 0.4, 0.8 or 1.6 nmol injections of 8-OH-DPAT. Additional 90 min measures of intake were also made after 0 vs. 250 microg (760 nmol) 8-OH-DPAT s.c. At the two highest DRN doses tested, lesioned rats showed 50% less intake compared to shams. A similar profile emerged after the single s.c. dose. These results suggest that the PDA may be an important locus at which reduced release of endogenous 5-HT stimulates feeding. Alternatively, the PDA may represent part of a larger brain circuit whose integrity is necessary for eliciting intake in response to a variety of feeding stimuli.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Comparison of the relative effects of 1,24-dihydroxyvitamin D(2) [1, 24-(OH)(2)D(2)], 1,24-dihydroxyvitamin D(3) [1,24-(OH)(2)D(3)], and 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] on selected vitamin D-regulated events in the rat.

The present experiments were conducted to compare the relative hypercalciuric and hypercalcemic activities of 1,24-dihydroxyvitamin D(2) [1,24-(OH)(2)D(2)], 1,24-dihydroxyvitamin D(3) [1, 24-(OH)(2)D(3)], and 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] in 7-week-old rats. The rats were dosed orally with each sterol for 7 days at a rate of 1 ng/g body weight/day. We also monitored the effect of the three compounds on the induction of mRNA for CaATPase and for 25-hydroxyvitamin D-24-hydroxylase in the kidney and intestine, on plasma vitamin D metabolite levels, and on the capacity to evoke modification in the vitamin D receptor/retinoic acid X receptor (VDR/RXR) heterodimer conformation. Plasma calcium was elevated in the rats treated with 1,24-(OH)(2)D(3) and 1, 25-(OH)(2)D(3), but not in the 1,24-(OH)(2)D(2)-dosed rats. Urinary calcium was elevated significantly (relative to controls) in all groups. The order of hypercalciuric activity was 1,25-(OH)(2)D(3) >/= 1,24-(OH)(2)D(3) >/= 1,24-(OH)(2)D(2) > control. Duodenal plasma membrane calcium ATPase (PMCA) mRNA was elevated to a similar extent in all groups relative to controls. Duodenal 24-hydroxylase mRNA was elevated in all groups relative to controls; however, the elevations were significantly higher in the 1,24-(OH)(2)D(3) and 1, 25-(OH)(2)D(3) groups compared with the 1,24-(OH)(2)D(2) group. Kidney 24-hydroxylase also was elevated significantly in the 1, 24-(OH)(2)D(3)- and 1,25-(OH)(2)D(3)-treated rats but not in the 1, 24-(OH)(2)D(2)-treated rats. Recombinant human vitamin D receptor (hVDR) extracts were incubated with saturating concentrations of 1, 24-(OH)(2)D(2), 1,24-(OH)(2)D(3), and 1,25-(OH)(2)D(3) and subsequently analyzed by electrophoretic mobility shift assay (EMSA). Overall binding was comparable for all metabolites; however, the 1, 24-(OH)(2)D(2) complex exhibited distinctly altered mobility relative to 1,24-(OH)(2)D(3) and 1,25-(OH)(2)D(3), suggestive of an effect on hVDR/hRXR conformation. These data suggest that 1, 24-(OH)(2)D(2) is not as potent as either of the vitamin D(3) sterols at affecting hypercalcemia or hypercalciuria in young growing rats; however, 1,24-(OH)(2)D(2) can evoke other biological responses similar to the vitamin D(3) sterols. These different responses may be related to the alterations in conformation state of the hVDR/hRXR heterodimer.

Analysis of Variance↗
PubMed2000

Effects of three neurochemical stimuli on delayed feeding and energy metabolism.

Infusions of norepinephrine (NE), the gamma-aminobutyric acid agonist, muscimol (MUS), or neuropeptide Y (NPY) into the paraventricular nucleus (PVN) of the hypothalamus all increase food intake. Such feeding may be due to direct activation of behavioral processes driving ingestion and/or to alterations in nutrient metabolism that feeding serves to normalize. To examine these possibilities, male Sprague-Dawley rats received PVN infusions of vehicle, 20 nmol NE, 1 nmol MUS or 100 pmol NPY at dark onset, then food intake was measured under three feeding conditions: (1) 1 and 2 h immediately after injections, (2) 1 h after a 1 h delay between injections and access to food, and (3) 1 h after a 1 h feeding delay, but with injections occurring just before presenting food. Measures of energy expenditure (EE) and respiratory quotients (RQs) in the absence of food were made over 2 h in parallel experiments. Results confirmed that NE, MUS and NPY all increased dark-onset feeding, but only NPY increased intake above control levels after a 1 h feeding delay. No neurochemically-induced changes in EE were observed, nor were there changes in RQs after NE or MUS. However, NPY reliably enhanced RQs from 30 to 120 min of testing. Our findings imply that NE and MUS initiate relatively immediate, short-term feeding that is not associated with changes in nutrient metabolism and does not summate with cues stimulated by delayed access to food. NPY initiates more protracted feeding temporally linked to enhanced carbohydrate metabolism. This may indicate that part of NPY's feeding stimulatory effects are secondary to physiological processes driving ingestion.

Animals↗
PubMed2000

Imposed vibration influences perceived tactile smoothness.

According to the duplex theory of tactile texture perception, detection of cutaneous vibrations produced when the exploring finger moves across a surface contributes importantly to the perception of fine textures. If this is true, a vibrating surface should feel different from a stationary one. To test this prediction, experiments were conducted in which subjects examined two identical surfaces, one of which was surreptitiously made to vibrate, and judged which of the two was smoother. In experiment 1, the vibrating surface was less and less often judged smoother as the amplitude of (150 Hz) vibration increased. The effect was comparable in subjects who realized the surface was vibrating and those who did not. Experiment 2 showed that different frequencies (150-400 Hz) were equally effective in eliciting the effect when equated in sensation level (dB SL). The results suggest that vibrotaction contributes to texture perception, and that, at least within the Pacinian channel, it does so by means of an intensity code.

Adolescent↗
PubMed1999

Lay health advisor activity levels: definitions from the field.

One type of lay health advisor model assumes that an effective mechanism for reaching the underserved is through informal advice-givers called natural helpers. Despite the growing use of this approach, few programs have defined what an active lay health advisor does within the natural helping process. To explore perceptions and definitions of lay health advisors' activity, we conducted semistructured, in-person interviews with four field staff who coordinate the advisors' activities in a breast cancer screening program. These staff viewed lay health advisor activity as fluctuating over the course of a year, occurring along a continuum of participation (inactive, moderately active, active, and superactive), and reflecting varying degrees of proactivity and participation in multiple activities. These results suggest an empirical process for refining the definition of an active lay health advisor, improving advisors' productivity in achieving outreach objectives, and managing and monitoring their ongoing activities.

Breast Neoplasms↗
PubMed1999

Inter-observer variation. An alternative method of assessing the role of ultrasonic imaging in clinical decision-making in lower limb arterial disease.

BACKGROUND: The aim of the study is to determine the role of duplex scanning in deciding on the final treatment for patients with lower limb arterial disease compared to intra-arterial digital subtraction arteriography (IA DSA). METHODS: Eighty-two patients (55 males, 27 females, mean age 68 years) with lower limb arterial disease had both duplex and arteriography performed. The findings of both modalities were reported by sonographer and radiologist in 164 anonymous reports. Five vascular surgeons (consultant grade) were asked to plan their treatment on the data provided in these reports. For the purposes of statistical analysis, the actual treatment the patient received was used as the reference standard. Both reports and treatment decisions were coded (double blinded). RESULTS: The overall accuracy of duplex scanning to assess arterial disease of the lower limbs showed a sensitivity of 92%, and specificity of 99%. The accuracy of the decisions based on duplex was 84% and kappa with k of 0.62 (95% CI+0.14) compared to the reference standard, while the accuracy of the decision based on arteriography was 85% and kappa 0.63 (95% CI+0.14). The accuracy of decisions based on duplex compared to those based on arteriography (arteriography used as reference standard) was 91% and a kappa of 0.77 (95% CI+0.14). CONCLUSIONS: Duplex scanning is an accurate diagnostic modality, and clinical decisions can be safely based on its findings.

Aged↗
PubMed1997

Gene sequence, localization, and evolutionary conservation of DAZLA, a candidate male sterility gene.

We have isolated the human homologue of the mouse germ cell-specific transcript Tpx2, which we had previously mapped to mouse chromosome 17. Sequence analysis shows that the human gene is part of the DAZ (Deleted in Azoospermia) family, represents the human homologue of the mouse Dazla and Drosophila boule genes, and is termed DAZLA. Like Dazla and boule, DAZLA is single copy and maps to 3p25. This defines a new region of synteny between mouse chromosome 17 and human chromosome 3. Unlike DAZ, which has multiple DAZ repeats, DAZLA encodes a putative RNA-binding protein with a single RNA-binding motif and a single DAZ repeat. DAZLA is more closely related to Dazla in the mouse than to the Y-linked homologue DAZ (88% identity overall with mouse Dazla compared to 76% identity with the human DAZ protein sequence). Southern blot analysis showed that DAZLA is autosomal in all mammals tested and that DAZ has been recently translocated to the Y chromosome, sometime after the divergence of Old World and New World primates. To investigate the evolutionary relatedness of DAZLA and DAZ further, their partial genomic structures were obtained and compared. This revealed that the genomic organization of both genes in the 5' region is highly conserved. DAZLA is a new member of the DAZ family of genes, which is associated with spermatogenesis and male sterility. Familial cases of male infertility in humans show an autosomal recessive mode of inheritance. It is possible that some of these families may carry mutations in the DAZLA gene.

Amino Acid Sequence↗
PubMed1997

Alerting effects of methylphenidate under basal and sleep-deprived conditions.

Six men and 3 women on each of 4 days received 10 mg of methylphenidate or placebo (2 times a day) at 0800 and 1200 after 8 hr or 0 hr of sleep. Sleep latency was measured by the Multiple Sleep Latency Test (MSLT) at 0930, 1130, 1330, 1530, and 1730. Participants also completed divided-attention and auditory vigilance tasks at 1000 and 1400 and the Profile of Mood States (POMS) and the Addiction Research Center Inventory (ARCI) after the 0930 and 1330 latency tests. The drug increased mean latency on the MSLT in both sleep conditions. Performance only showed drug effects after prior sleep deprivation. On the POMS, the drug increased Vigor and reduced Fatigue and Depression scale scores, primarily after sleep deprivation. The drug increased the ARCI Amphetamine and Morphine-Benzedrine scores only in the basal state. The ARCI Pentobarbital score was increased by sleep deprivation and decreased by the drug.

Adult↗
PubMed1997

The alerting effects of short and long naps in narcoleptic, sleep deprived, and alert individuals.

Eleven narcoleptic patients and 22 age- and gender-matched normal controls participated in a study to determine the alerting effects of differing nap lengths. All narcoleptic patients had been previously diagnosed [mean sleep latency on the multiple sleep latency test (MSLT) < or = 5 minutes with two or more sleep-onset rapid eye movement periods (SOREMPs)]. Healthy, normal subjects with a mean sleep latency on the screening MSLT > or = 8 minutes were randomly assigned to one of two groups (i.e. sleep-deprived and alert). All subjects completed two experimental night and days with at least 5 days between sessions. On the evening prior to each experimental day, narcoleptic and alert subjects spent 8 hours in bed and sleep-deprived subjects spent 0 hours in bed. The following day, all subjects underwent one of two napping conditions, 15 or 120 minutes in bed. Both naps were terminated at noon. Every subject underwent both conditions and the order of conditions was counterbalanced. From 1215 to 1355 hours all subjects underwent a modified MSLT. At 1500 hours, the subjects had a 1-hour nap. The results showed that the 120-minute nap condition was more beneficial than the 15-minute nap. Narcoleptic and sleep deprived subjects were shown to have comparable levels of sleepiness on the modified MSLT. However, a differential response pattern on their latency to sleep was noted on the 1-hour nap. Sleep-deprived subjects were shown to be differentially more alert following a 120-minute nap opportunity. In contrast, for narcoleptic patients the beneficial effects of the nap were lost when tested 3 hours later. These results show that narcoleptic patients benefit from a longer nap but that these benefits are short-lived.

Adult↗
PubMed1997

The sleep/wake habits of patients diagnosed as having obstructive sleep apnea.

STUDY OBJECTIVE: To determine the sleep/wake habits of patients diagnosed as having obstructive sleep apnea (ie, respiratory event index [REI] > or = 5). DESIGN: Case series with prospective data collection to determine the relationship among sleepiness, REI, and sleep/wake habits. Patients were grouped according to their multiple sleep latency test (MSLT) results (< or = 5 and > 5) and REI (mild REI < or = 20; moderate REI > 20 but < or = 60; and severe REI > 60). SETTING: An American Sleep Disorders Association-accredited sleep laboratory. PATIENTS: Three hundred ninety (325 male, 65 female) consecutive patients seen between June 1993 and January 1995 for evaluation of sleep apnea. This included a sleep, medical, and psychiatric evaluation followed by a physical examination. Sleep histories and sleep/wake habits were recorded by a physician trained in sleep medicine. Polysomnographic evaluation consisted of a nocturnal clinical polysomnogram (CPSG) and an MSLT on the following day. Of 390 patients, 268 completed polysomnographic evaluation (CPSG and MSLT). MEASUREMENTS AND RESULTS: Sleepy (MSLT < or = 5) patients with mild (REI < or = 20) and moderate apnea (REI > 20 < or = 60) reported spending significantly less time in bed than sleepy patients with severe apnea (REI > 60). Those with severe apnea (REI > 60) reported napping significantly more and experienced a more severe disruption of their routine daily activities because of sleepiness when compared with mild and moderate OSA patients. CONCLUSIONS: These data suggest that sleep habits have an important modulatory effect on the level of sleepiness and this effect is lost as the severity of sleep-disordered breathing increases.

Aging↗
PubMed1997

The effects of predetermined payment rates for Medicare home healthcare.

OBJECTIVE: To assess the effects of an alternative method of paying home health agencies for services to Medicare beneficiaries, based on a demonstration program. DATA SOURCES/STUDY SETTING: Primary and secondary data collected on participating home health agencies in five states and their patients during the three-year demonstration period. Primary data included patient surveys at discharge and six months later, and two rounds of interviews with executive staff of the agencies. Secondary data included agencies' Medicare cost reports, quality assurance reviews, Medicare claims data, demonstration claims data, demonstration patient intake forms, and plan of treatment forms. STUDY DESIGN: The 47 agencies volunteering to participate in the demonstration were each randomly assigned to the treatment or control group. Treatment group agencies were paid a predetermined rate based on their inflation-adjusted cost per visit during the year preceding the demonstration; control group agencies were paid under Medicare's conventional cost reimbursement method. Demonstration impacts were estimated by comparing outcomes for the two groups of agencies and their respective patients, using regression models to control for any remaining differences. PRINCIPAL FINDINGS: Agencies paid under prospective rate setting were slightly better at holding per-visit cost increases below inflation than were control group agencies. The change in payment method had no effect on agencies' volume of Medicare visits or quality of care, nor on patients' use of Medicare services or other formal or informal care services. CONCLUSION: Changing from cost-based reimbursement to predetermined payment rates for Medicare home healthcare visits would not lead to large savings for the Medicare program, but would not increase costs to Medicare or adversely affect patients or their caregivers.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1997

A hidden complication of out-patient arteriography.

Rapid progression of arterial disease may occur between out-patient diagnostic arteriography and therapeutic angioplasty. We have studied the incidence of this complication in our institution. Sixty-seven consecutive out-patient arteriograms were assessed. Thirty-four patients were re-admitted for angioplasty within a median interval of 4 weeks (range 5 days-3 months). We compared immediate pre-angioplasty arteriograms with the out-patient images. Twenty-five pairs of films showed disease progression. Three patients showed new disease, one remote from the site of the arterial lesion and two in the opposite limb. Six patients showed marked progression of the original disease. The policy of delayed treatment after out-patient arteriography may require reconsideration in the light of our complication rate of 18%.

Aged↗
PubMed1996

Nocturnal sleep latencies among alert, alert-deprived and sleepy subjects.

Twenty-seven healthy, asymptomatic subjects participated in a study to determine repeated nocturnal sleep latencies as a function of level of daytime sleepiness. Subjects were screened polysomnographically and were determined to be free of any sleep pathology. Nine subjects had a screening multiple sleep latency test (MSLT) of < or = 5 min and 18 had a MSLT of > or = 10 min. Subjects were assigned to 3 groups, sleepy (MSLT < or = 5 min), alert, and alert sleep-deprived groups (MSLT > or = 10 min). Repeated nocturnal latencies to sleep were determined at 2300, 0110, 0310 and 0510 h on 2 nights with at least 5 days between nights. The results showed a main effect of group on the repeated nocturnal sleep latencies. Post-hoc tests demonstrated longer repeated nocturnal latencies among alert subjects compared to the sleepy and alert sleep-deprived subjects. The latter two groups had comparable sleep latencies. A significant main effect of time of night was also shown. The 0510 h latency was significantly shorter than the latencies at 2300 and 0110 h. The 0310 h latency was significantly shorter than the 0110 h latency and comparable to the 2300 and 0510 h latency. Significant correlations were found between daytime MSLT, repeated nocturnal sleep latencies, and nocturnal sleep time. These results show systematic differences in repeated nocturnal sleep latencies among sleep and alert subjects and extend the already described characteristics of these subjects by comparing them to a group of alert sleep-deprived subjects.

Adult↗